The research line heart muscle cell formation focuses on heart muscle cell formation after development of the linear heart tube. A 3-dimensional gel lattice in vitro explant system has been developed in which heart muscle and epicardial development can be mimicked, manipulated and analyzed using confocal laser scanning microscopy. In vitro and in vivo heart development is influenced by applying growth factors and/or using recombinant adenoviruses, which are produced within the group, in the pericardial cavity. An extensive collection of constitutive active and dominant negative acting components of the BMP signaling pathway have been developed. The influences on heart development are analyzed using non-radioactive in situ hybridization, immunohistochemistry and quantitative 3D automated reconstruction methods. Heart muscle formation by myocardialization in the outflow tract is analyzed using a combined PCR-based subtraction and array method and heart muscle cell formation at the level of the proepicardium is investigated using in vitro arrays and microarrays.
Currently research focuses on heart muscle cell formation at the inflow of the heart, at the level of the proepicardium. Candidate gene analysis have identified an integrated role of BMP and FGF signalling, which is being pursued. An extensive genome wide analysis using chicken microarrays has been initiated to identify genes involved in heart muscle cell formation. The initial genome wide analysis has identified a potential regulator of myocardialization of which a global and conditional knock-out mouse has been made and is being analyzed.
Effective start/end date01/01/2007 → …

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